Receptors for luminal small organic molecules and gases

The Receptors for luminal small organic molecules and gases represent a specialized group of G protein-coupled receptors (GPCRs) and other sensory proteins that detect chemical signals within the lumen of the gastrointestinal tract, airways, and other mucosal environments [1]. This category includes receptors for short-chain fatty acids (e.g., FFA2 and FFA3), bile acids (e.g., TGR5), and various microbial metabolites such as kynurenic acid and lactate [2][3]. Additionally, it encompasses sensors for gasotransmitters like nitric oxide, hydrogen sulfide, and carbon monoxide, which are critical for regulating local blood flow, immune responses, and epithelial integrity [4]. These receptors serve as a vital interface between the external environment—including the gut microbiota—and host physiological systems, influencing metabolism, inflammation, and gut motility [5]. While this grouping is used in pharmacological databases like the IUPHAR/BPS Guide to Pharmacology to categorize chemosensors, it does not refer to a single therapeutic target but rather a diverse family of proteins [1]. Drugs targeting these pathways, such as bile acid sequestrants, SCFA analogs, and gas-releasing prodrugs, are currently used or under investigation for treating metabolic syndrome, inflammatory bowel disease, and cardiovascular disorders [6].

Other names

Luminal chemosensorsMetabolite-sensing GPCRsGut-nutrient receptorsGas-sensing receptorsLuminal ligands

Molecules in this category act as endogenous ligands or substrates for a variety of receptors (primarily GPCRs and nuclear receptors) and enzymes, modulating cellular signaling pathways related to inflammation, metabolism, and vascular tone.